Life Extension Magazine®

Woman using three peptides to target wrinkles from decline in skin elasticity

Issue: Apr 2014

Target Wrinkle Formation with Novel Peptides

Fine lines and wrinkles occur when environmental factors overwhelm the body’s ability to maintain critical biochemical processes, resulting in DNA damage and loss of skin elasticity. Scientists have discovered three peptides that work within skin cells to inhibit this aging effect. Studies show a 28% reversal in the appearance of deep wrinkles within minutes, with results continuing for months.

Scientifically reviewed by: Dr. Carol Campi, RN, DC, in May 2022. Written by: Robert Goldfaden and Gary Goldfaden, MD.

Target Wrinkle Formation with Novel Peptides  

We often think of wrinkles as an inevitable part of aging. But it doesn’t have to be that way.

Fine lines and wrinkles occur when certain processes in the body break down, leading to DNA damage and the destruction of skin firmness and elasticity.

Scientists have discovered three powerful peptides that target the underlying causes of wrinkle formation—and help restore your body’s ability to fight wrinkles from the inside out.

This leads to visible results, with human studies demonstrating a 20% decrease in fine lines and a 28% decrease in deep wrinkles within minutes—results that continued to improve over the next few months.1

In this article, you will learn how a trio of peptides works to diminish the appearance of fine lines and unsightly wrinkles to reveal smoother, firmer, more youthful-looking facial skin.

Enhanced DNA Repair Capacity

DNA damage to your skin is inevitable due to both environmental factors and internal aging. The difference between younger and older skin is that younger skin has support systems in place that help repair the damage and prevent premature skin aging.

Younger, healthy skin responds to damaged DNA by stimulating an important element called transcriptional factor forkhead-box protein O3a (FOXO3a). 2 This turns on genes that support cell repair, renewal, and longevity.2,3 This process is critical for preserving DNA integrity and maintaining accurate replication of genetic material.

As you age, the decline in FOXO3a activity reduces the capacity of cells to repair themselves and contributes to the accumulation of DNA damage.4 The result is a domino effect that decreases gene expression favoring skin functionality and quality, while simultaneously increasing gene expression that damages the skin’s key components. This gradual process degrades both the skin’s collagen and elastin,5 which ultimately results in the creation of unwanted fine lines and wrinkles.

A newly developed compound called acetyl hexapeptide-51 has been shown to mimic the actions associated with FOXO3a activity—helping to protect the skin from the consequences of DNA damage.3 In the laboratory, human skin cells treated with this ingredient switched on the same beneficial genes as FOXO3a and produced a 2.7 fold increase in DNA repair pathway activity compared to a control.3

Positive results were seen in humans as well. When researchers topically applied acetyl hexapeptide-51 to the skin of 21 human volunteers after exposure to ultraviolet light, they observed 13.7% less DNA damage than the controls.3 And this effect was evident in just 6 hours!

Together, these studies suggest that acetyl hexapeptide-51 could combat wrinkle formation by enhancing DNA repair capacity and reducing the accumulation of DNA damage.

Improved Skin Cohesion And Firmness

Improved Skin Cohesion And Firmness  

Collagen and elastin are vital components of the dermal extracellular matrix that maintains skin cohesion, firmness, and elasticity.6 A balance exists between the breakdown and replenishment of skin structural proteins such as collagen and elastin. However, the natural decrease in the production of collagen and elastin that occurs during aging—along with chronic exposure to external factors like sunlight—creates an imbalance that promotes premature skin aging.7-9

One of the main reasons elastin production decreases as we age is due to diminishing levels of the enzymes lysyl oxidase-like 1 (LOXL1) and glycoprotein fibulin-5 (FBLN5).10,11 This decrease hinders the formation of elastin, which will gradually lead to disorganization in the ultrastructure of the extracellular matrix that maintains skin’s firmness and elasticity.12

The peptide acetyl tetrapeptide-2 has been discovered to increase the prevalence of LOXL1 by 1.7 fold and FBLN5 by 2.3 fold when exposed to human skin fibroblasts.13 Additional in-vitro tests showed a significant improvement in elastin synthesis by 21.7%.13

This suggests that when we combine the topical use of acetyl tetrapeptide-2—along with the effort to minimize external and environmental factors—we can help restore the normal balance between the formation and breakdown of elastin.

In a human study, scientists recruited 19 volunteers aged 50-60 with saggy facial skin to determine how effective acetyl tetrapeptide-2 would be at improving the firmness of the skin.13 Participants applied the ingredient to their face twice daily for 55 days. The results revealed a 9.5% reduction in indentation and a 23.2% decrease in area parameters.13 In other words, participants finished the study with visibly firmer and tighter facial skin than before treatment.

Scientists also discovered acetyl tetrapeptide-2’s additional benefits: It increases the formation of type I collagen by 47%, and it enhances the production of cellular adhesion molecules that coordinate the binding of cells to the dermal extracellular matrix— all of which reinforces skin cohesion and firmness.13

What You Need to Know
Rejuvenate Aging Skin

Rejuvenate Aging Skin

  • The dermal extracellular matrix (ECM) surrounds cells and contains the vital proteins elastin and collagen, which maintain skin cohesion, firmness, and elasticity.
  • Three powerful peptides work to diminish the appearance of fine lines and unsightly wrinkles to reveal smoother, firmer, youthful-looking facial skin by targeting the underlying causes of wrinkle formation.
  • Acetyl hexapeptide-51 produces a 2.7 fold increase in DNA repair pathways when exposed to human skin cells, resulting in 13.7% less DNA damage in controlled trials.
  • Acetyl tetrapeptide-2 increases skin firmness in human volunteers with saggy skin.
  • Palmitoyl tripeptide-5 regenerates collagen, and in a controlled human study significantly improved crow’s feet and wrinkles around the mouth within minutes!1

Potent Anti-Wrinkle Activity In Humans

Potent Anti-Wrinkle Activity In Humans  

Since collagen is the most abundant structural protein in the dermal extracellular matrix, the loss of collagen leads to changes in the matrix that accelerate aging and formation of wrinkles.7 One way to help prevent wrinkles is by preserving and renewing collagen.

The ingredient palmitoyl tripeptide-5 has been shown to stimulate collagen renewal through activation of latent tissue growth factor-b (TGF-b).1

In one study 37 women between 33 and 45 years old applied a cream containing palmitoyl tripeptide-5 twice daily to their crow’s feet and to the wrinkles around their mouth for three months.1 Scientists measured both fine and deep wrinkles in both of these regions at baseline, within 15 minutes, month one, and month three after application.

Researchers observed that within minutes, treatment of wrinkles around the eyes with palmitoyl tripeptide-5 decreased fine lines by an average of 20% and deep wrinkles by an average of 28%.1 After three months, these parameters further improved to 38% and 50%, thereby demonstrating the immediate and long-lasting anti-wrinkle effects of palmitoyl tripeptide-5.1

Immediate results were also noted for wrinkles around the mouth, and after three months participants experienced a 31% reduction in deep wrinkles and a 53% decrease in fine wrinkles.1

Scientists concluded that a topical treatment containing palmitoyl tripeptide-5 “produced significant improvements in facial wrinkles and provides a well-tolerated, no-downtime alternative to invasive procedures.”1


Fine lines and wrinkles do not have to be an inevitable part of aging. A trio of unique peptides, including acetyl hexapeptide-51, acetyl-tetrapeptide-2, and palmitoyl tripeptide-5, serves to naturally reduce the appearance of fine lines and wrinkles by enhancing DNA repair capacity and regenerating vital dermal extracellular matrix components.1,3,13 This restores skin cohesion, elasticity, and firmness—all of which work to diminish the appearance of wrinkles and preserve the skin’s youthful appearance.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.


  1. Trookman, NS, Rizer RL, Ford R, Ho E, Gotz V. Immediate and long-term clinical benefits of a topical treatment for facial lines and wrinkles. J Clin Aesthet Dermatol. 2009 Mar;2(3):38-43.
  2. Tran H, Brunet A, Greiner JM, et al. DNA repair pathways stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein. Science. 2002;296(5567):530-4.
  3. Product monograph: JuvefoxoTM. Lipotec. May 2013.
  4. Kim HK, Kim YK, Song I-H, et al. Down-regulation of a forkhead transcription factor, FOXO3a, accelerates cellular senescence in human dermal fibroblasts. J Gerontol. 2005;60(1):4-9.
  5. Dong KK, Damaghi N, Picart SD, et al. UV-induced DNA damage initiates release of MMP-1 in human skin. Exp Dermatol. 2008 Dec;17(12):1037-44.
  6. Available at: Accessed January 15, 2014.
  7. Quan T, Qin Z, Xia W, Shao Y, Voorhees JJ, Fisher GJ. Matrix-degrading metalloproteinases in photoaging. J Investig Dermatol Symp Proc. 2009 Aug;14(1):20-4.
  8. Varani J, Dame MK, Rittie L, et al. Decreased collagen production in chronologically aged skin: roles of age-dependent alteration in fibroblast function and defective mechanical stimulation. Am J Pathol. 2006 Jun;168(6):1861-8.
  9. Rossetti D, Kielmanowicz MG, Vigodman S, et al. A novel anti-ageing mechanism for retinol: induction of dermal elastin synthesis and elastin fibre formation. Int J Cosmet Sci. 2011 Feb;33(1):62-9.
  10. Cenizo V, Andre V, Reymermier C, et al. LOXL as a target to increase the elastin content in adult skin: a dill extract induces the LOXL gene expression. Exp Dermatol. 2006;15:574-81.
  11. Chapman SL, Sicot FX, Davis EC, et al. Fibulin-2 and fibulin-5 cooperatively function to form the internal elastic lamina and protect from vascular injury. Arterioscler Thromb Vasc Biol. 2010 Jan;30(1):68-74.
  12. Braverman IM. Elastic fiber and microvascular abnormalities in aging skin. Dermatol Clin. 1986 Jul;4(3):391-405.
  13. Product monograph: UplevityTM. Lipotec. June 2013.